Electroporation

Electroporation (electropermeabilization) is the creation of aqueous pores in lipid bilayers by the application of a short (microseconds to milliseconds) high voltage (200-1000V) electric pulse. It appears that electroporation occurs in the intercellular lipid bilayers of the stratum corneum by a mechanism involving transient structural changes11. Although DNA introduction is the most common use for electroporation, it has been used on isolated cells for introduction of enzymes, antibodies, and viruses, and more recently, tissue electroporation has begun to be explored, with potential applications including enhanced cancer tumour chemotherapy, gene therapy and transdermal drug delivery.

As presently understood, electroporation is an essentially universal membrane phenomenon that occurs in cell and artificial planar bilayer membranes. For short pulses (ps to ms), electroporation occurs if the transmembrane voltage reaches 0.5-1.5 V. Due to the small size of the cells it is necessary to apply a much higher voltage to a bulk sample in order to achieve this transmembrane voltage. In the case of isolated cells, the pulse magnitude is 103-104 V/cm. These pulses cause the formation of pores through the corneocyte which are initially only a few nanometres in diameter but enlarge as the current continues to flow. It is possible that electrical (Joule) heating increases the temperature in the channel sufficiently to melt the skin lipids and increase their permeability, in addition to forming aqueous pores59. This is accompanied by a large increase in molecular transport across the membrane. Membrane recovery can be orders of magnitude slower and cells can remain permeable for several minutes after the pulse or longer. It is likely that, in addition to forming aqueous pores in the skin epithelium, the electric field opens the appendageal route, although the relative importance of these pathways is not yet clear60. An associated cell stress commonly occurs, probably because of chemical influxes and effluxes leading to chemical imbalances, which may lead to cell death61. A detailed discussion of the electrical and structural changes involved in electroporation is given by Teissie et al62.

Electroporation has been used to deliver a wide range of drugs with molecular weights up to several thousand daltons63 and leads to an increase in permeability up to 4 orders of magnitude. Absorption is significantly higher if the field is in the 'forward' direction with respect to the drug being delivered, i.e. if the drug is cationic the electrode should be positive with respect to the skin, and vice versa for an anionic drug.

Combinations of electroporation with iontophoresis64 and with ultrasound65 have been demonstrated to provide further increases in drug flux over electroporation alone, and a number of macromolecules also appear to increase flux, possibly by stabilizing the transient pores in the skin66.

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